The SIV model (both in vitro and in vivo) is excellent for testing HIV drug therapies owing to the similarities between SIVmne and HIV in structure, genomic organization, and disease production. The goal of this project is to develop an effective antiviral therapy to either prevent or cure AIDS in macaques. Ultimately, this information may be applied to AIDS in humans. In 1997 we continued a clinical trial using preexposure and postexposure prophylaxis of an acyclic nucleoside phosphonate, (R)-9-(2-phosphonylmethoxyethl)adenine (PMPA), against acute SIV infection in longtailed macaques. PMPA prevented the establishment of SIV infection when a 28-day treatment was initiated 24 h after intravenous virus inoculation with SIV (100% infectious dose). All untreated, inoculated macaques became infected with SIV.